Validation and Safety Profile of a Novel, Noninvasive Fiducial Attachment for Stereotactic Robotic-Guided Stereoelectroencephalography: A Case Series.

BACKGROUND AND OBJECTIVES: We developed, tested, and validated a novel, noninvasive, Leksell G frame-based fiducial attachment, for use in stereotactic registration for stereoelectroencephalography (sEEG). Use of the device increased the number of fixed reference points available for registration, while obviating the need for additional scalp incisions. We report here on our experience and safety profile of using the device. METHODS: We collected registration data using the fiducial device across 25 adult and pediatric patients with epilepsy consecutively undergoing robotic-guided sEEG for invasive epilepsy monitoring, treated between May 2022 and July 2023. ROSA One Brain was used for trajectory planning and electrode implantation. Postoperative clinical and radiographic data were computed and quantified, including mean registration error for all patients. Entry point, target point (TP), and angular errors were measured. Descriptive statistics and correlation coefficients for error were calculated. RESULTS: Twenty-five patients underwent robotic-guided sEEG implantation (11 patients, bilateral; 10 patients, left unilateral; 4 patients, right). The mean number of electrodes per patient was 18 ± 3. The average mean registration error was 0.77 ± 0.11 mm. All patients were implanted with Ad-Tech depth electrodes. No clinically relevant complications were reported. Analysis of trajectory error was performed on 446 electrodes. The median entry point error was 1.03 mm (IQR 0.69-1.54). The median TP error was 2.26 mm (IQR 1.63-2.93). The mean angular error was 0.03 radians (IQR 0.02-0.05). There was no significant correlation between root mean square error and lead error. Root mean square error did not appreciably change over time, nor were there any significant changes in average angular, entry point, or TP error metrics. CONCLUSION: A novel, noninvasive, Leksell G frame-based fiducial attachment was developed, tested, and validated, facilitating O-arm-based stereotactic registration for sEEG. This simple innovation maintained an excellent accuracy and safety profile for sEEG procedures in epilepsy patients, with the added advantages of providing additional reference points for stereotactic registration, without requiring additional scalp incisions.

Cognitive phenotypes in frontal lobe epilepsy.

OBJECTIVE: Neuropsychological profiles are heterogeneous both across and within epilepsy syndromes, but especially in frontal lobe epilepsy (FLE), which has complex semiology and epileptogenicity. This study aimed to characterize the cognitive heterogeneity within FLE by identifying cognitive phenotypes and determining their demographic and clinical characteristics. METHOD: One hundred and six patients (age 16-66; 44% female) with FLE completed comprehensive neuropsychological testing, including measures within five cognitive domains: language, attention, executive function, processing speed, and verbal/visual learning. Patients were categorized into one of four phenotypes based on the number of impaired domains. Patterns of domain impairment and clinical and demographic characteristics were examined across phenotypes. RESULTS: Twenty-five percent of patients met criteria for the Generalized Phenotype (impairment in at least four domains), 20% met criteria for the Tri-Domain Phenotype (impairment in three domains), 36% met criteria for the Domain-Specific Phenotype (impairment in one or two domains), and 19% met criteria for the Intact Phenotype (no impairment). Language was the most common domain-specific impairment, followed by attention, executive function, and processing speed. In contrast, learning was the least impacted cognitive domain. The Generalized Phenotype had fewer years of education compared to the Intact Phenotype, but otherwise, there was no differentiation between phenotypes in demographic and clinical variables. However, qualitative analysis suggested that the Generalized and Tri-Domain Phenotypes had a more widespread area of epileptogenicity, whereas the Intact Phenotype most frequently had seizures limited to the lateral frontal region. SIGNIFICANCE: This study identified four cognitive phenotypes in FLE that were largely indistinguishable in clinical and demographic features, aside from education and extent of epileptogenic zone. These findings enhance our appreciation of the cognitive heterogeneity within FLE and provide additional support for the development and use of cognitive taxonomies in epilepsy.

Management Strategies for Large Brain Metastases.

Brain metastases represent the most common intracranial neoplasm and pose a significant disease burden on the individual and the healthcare system. Although whole brain radiation therapy was historically a first line approach, subsequent research and technological advancements have resulted in a larger armamentarium of strategies for treatment of these patients. While chemotherapeutic options remain limited, surgical resection and stereotactic radiosurgery, as well as their combination therapies, have shifted the paradigms for managing intracranial metastatic disease. Ultimately, no single treatment is shown to be consistently effective across patient groups in terms of overall survival, local and distant control, neurocognitive function, and performance status. However, close consideration of patient and tumor characteristics may help delineate more favorable treatment strategies for individual patients. Here the authors present a review of the recent literature surrounding surgery, whole brain radiation therapy, stereotactic radiosurgery, and combination approaches.

Quality of life outcomes in patients presenting for evaluation of CNS tumors.

BACKGROUND: We describe patient-reported outcomes (PROs) in adults with CNS tumors and evaluate their correlation with physician-reported functional status. METHODS: We completed a retrospective cohort study of patients managed at a high-volume CNS tumor institute between September 2013 and September 2014. PROs were measured using 6 domains from the PROs Measurement Information System (PROMIS): anxiety, physical function, pain interference, sleep disturbance, fatigue, and satisfaction with social roles. Physician-reported outcomes were measured using the Eastern Cooperative Oncology Group Scale of Performance Status (ECOG). We compared differences in PROMIS scores across tumor types using analysis of variance and measured the correlation between PROMIS scores and ECOG scores using spearman correlations. Finally, we compared the range of PROMIS physical function scores within each ECOG level. RESULTS: In a cohort of 2,828 patients, 1,284 (45.4%) completed all 6 PROMIS domains. There were significant differences in PROMIS scores across tumor types for all domains except anxiety. The strength of the correlation between PROMIS and ECOG scores was weak to moderate for all PROMIS domains (all p < 0.001). The correlation was the strongest between the physical function domain and ECOG score (ρ = -0.54), although there was a broad distribution of physical function scores within ECOG level, with scores spanning nearly 5 SDs within most ECOG levels. CONCLUSIONS: Symptom burden was associated with tumor type. There were only weak to moderate correlations between PROMIS and ECOG scores, underscoring the importance of integrating PROs into clinical practice for patients with CNS tumors.

Upfront Magnetic Resonance Imaging-Guided Stereotactic Laser-Ablation in Newly Diagnosed Glioblastoma: A Multicenter Review of Survival Outcomes Compared to a Matched Cohort of Biopsy-Only Patients.

BACKGROUND: Laser ablation (LA) is used as an upfront treatment in patients with deep seated newly diagnosed Glioblastoma (nGBM). OBJECTIVE: To evaluate the outcomes of LA in patients with nGBM and compare them with a matched biopsy-only cohort. METHODS: Twenty-four nGBM patients underwent upfront LA at Cleveland clinic, Washington University in St. Louis, and Yale University (6/2011-12/2014) followed by chemo/radiotherapy. Also, 24 out of 171 nGBM patients with biopsy followed by chemo/radiotherapy were matched based on age (< 70 vs ≥ 70), gender, tumor location (deep vs lobar), and volume (<11 cc vs ≥11 cc). Progression-free survival (PFS), overall survival (OS), and disease-specific PFS and OS were outcome measures. Three prognostic groups were identified based on extent of tumor ablation by thermal-damage-threshold (TDT)-lines. RESULTS: The median tumor volume in LA (n = 24) and biopsy only (n = 24) groups was 9.3 cm3 and 8.2 cm3 respectively. Overall, median estimate of OS and PFS in LA cohort was 14.4 and 4.3 mo compared to 15.8 mo and 5.9 mo for biopsy only cohort. On multivariate analysis, favorable TDT-line prognostic groups were associated with lower incidence of disease specific death (P = .03) and progression (P = .05) compared to other groups including biopsy only cohort. Only age (<70 yr, P = .02) and tumor volume (<11 cc, P = .03) were favorable prognostic factors for OS. CONCLUSION: The maximum tumor coverage by LA followed by radiation/chemotherapy is an effective treatment modality in patients with nGBM, compared to biopsy only cohort. The TDT-line prognostic groups were independent predictor of disease specific death and progression after LA.

Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma.

The circulating levels of soluble tumor necrosis factor receptor-1 (sTNF-R1) and sTNF-R2 are altered in numerous diseases, including several types of cancer. Correlations with the risk of progression in some cancers, as well as systemic manifestations of the disease and therapeutic side-effects, have been described. However, there is very little information on the levels of these soluble receptors in glioblastoma (GBM). Here, we report on an exploratory retrospective study of the levels of sTNF-Rs in the vascular circulation of patients with GBM. Banked samples were obtained from 112 GBM patients (66 untreated, newly-diagnosed patients and 46 with recurrent disease) from two institutions. The levels of sTNF-R1 in the plasma were significantly lower in patients with newly-diagnosed or recurrent GBM than apparently healthy individuals and correlated with the intensity of expression of TNF-R1 on the tumor-associated endothelial cells (ECs) in the corresponding biopsies. Elevated levels of sTNF-R1 in patients with recurrent, but not newly-diagnosed GBM, were significantly associated with a shorter survival, independent of age (p = 0.02) or steroid medication. In contrast, the levels of circulating sTNF-R2 were significantly higher in recurrent GBM than healthy individuals and there was no significant correlation with expression of TNF-R2 on the tumor-associated ECs or survival time. The results indicate that larger, prospective studies are warranted to determine the predictive value of the levels of sTNF-R1 in patients with recurrent GBM and the factors that regulate the levels of sTNF-Rs in the circulation in GBM patients.

Evidence-based interventions to reduce shunt infections: a systematic review.

PURPOSE: Cerebrospinal fluid shunt infection is associated with patient morbidity and high cost. We conducted a systematic review of the current evidence of comprehensive surgical protocols or individual interventions designed to reduce shunt infection incidence. METHODS: A systematic review using PubMed and SCOPUS identified studies evaluating the effect of a particular intervention on shunt infection risk. Systemic prophylactic antibiotic or antibiotic-impregnated shunt efficacy studies were excluded. A total of 7429 articles were screened and 23 articles were included. RESULTS: Eight studies evaluated the effect of comprehensive surgical protocols. Shunt infection was reduced in all studies (absolute risk reduction 2.2-12.3 %). Level of evidence was low (level 4 in seven studies) due to the use of historical controls. Compliance ranged from 24.6 to 74.5 %. Surgical scrub with antiseptic foam and omission of a 5 % chlorhexidine gluconate preoperative hair wash were both associated with increased shunt infection. Twelve studies evaluated the effect of a single intervention. Only antibiotic-impregnated suture, a no-shave policy, and double gloving with glove change prior to shunt handling, were associated with a significant reduction in shunt infection. In a hospital with high methicillin-resistant staphylococcus aureus (MRSA) prevalence, a randomized controlled trial found that perioperative vancomycin rather than cefazolin significantly reduced shunt infection rates. CONCLUSION: Despite wide variation in compliance rates, the implementation of comprehensive surgical protocols reduced shunt infection in all published studies. Antibiotic-impregnated suture, a no-shave policy, double gloving with glove change prior to device manipulation, and 5 % chlorhexidine hair wash were associated with significant reductions in shunt infection.